JAK-STAT信号通路抑制剂在脊髓损伤后的作用机制

Mechanisms of JAK-STAT signaling pathway inhibitors after spinal cord injury

目的探讨JAK-STAT信号通路及其抑制剂在脊髓损伤后的作用机制。方法选择30只SD大鼠建立脊髓损伤模型,在手术后随机分为两组,每组15只,A组在造成脊髓损伤后腹腔注射生理盐水作为对照组,B组在造成脊髓损伤后腹腔注射JAK-STAT信号通路抑制剂作为实验组。观察两组在治疗后的运动功能障碍评分、脊髓损伤行为学评分(BBB评分),HE染色检测两组脊髓损伤的病理变化、Ki67免疫组化染色检测两组的细胞增殖表达情况,免疫荧光染色检测细胞核凋亡状态,流式细胞术检测细胞凋亡。结果建立脊髓损伤模型后,生理盐水组运动功能障碍评分与JAK-STAT信号通路抑制剂组比较,差异无统计学意义(P>0.05);JAK-STAT信号通路抑制剂组BBB评分优于生理盐水组(P<0.05)。Ki67免疫组化结果显示,与生理盐水组相比,JAK-STAT信号通路抑制剂组细胞增殖减少明显(P<0.05);免疫荧光染色及流式细胞术检测细胞凋亡结果显示,JAK-STAT信号通路抑制剂组凋亡细胞数目明显少于生理盐水组。结论JAK-STAT信号通路参与脊髓损伤的发生、发展,JAK-STAT信号通路抑制剂通过抑制细胞增殖和凋亡,减轻炎性反应进而减缓脊髓损伤,促进脊髓功能恢复。

Objective To investigate the mechanism of JAK-STAT after spinal cord injury.Methods Thirty Sprague Dawley rats were randomly divided into normal saline group and JAK stat inhibitor group,15 rats in each group.Saline group was injected intraperitoneally after spinal cord injury,and JAK stat inhibitor group was injected intraperitoneally after spinal cord injury.The motor dysfunction score and spinal cord injury behavior score(BBB score)of the two groups after treatment were observed.The pathological changes of spinal cord injury in the two groups were detected by HE staining.The proliferation and expression of Ki67 were detected by immunohistochemical staining.The nuclear apoptosis was detected by immunofluorescence,and the apoptosis was detected by flow cytometry.Results There was no significant difference in the scores of motor dysfunction between the two groups(P>0.05),but the BBB score of JAK stat inhibitor group was better than that of normal saline group(P<0.05).The results of Ki 67 immunohistochemistry showed that the proliferation of JAK stat inhibitor group was significantly lower than that of normal saline group(P<0.05).Flow cytometry showed that the number of apoptotic cells in JAK stat inhibitor group was significantly more than that in saline group(P<0.05).Conclusion Inhibitors of the JAK-Stat signaling pathway alleviates spinal cord injury by reducing cell proliferation and increasing apoptosis.